1. Field of the Invention
The present invention relates to semi-synthetic antifungal compounds, their therapeutic use, pharmaceutical compositions containing them, and methods for their preparation. More particularly, these antifungal compounds are derivatives of pradimicins.
2. Background Art
Pradimicins, also known as BU-3608 antibiotics, are a group of antifungal antibiotics produced by Actinomadura hibisca sp. nov. Various pradimicins that have been isolated from fermentation broths of Actinomadura hibisca or variants or mutants thereof, and their structures are depicted below: ##STR1##
Pradimicin
A: R.sup.1 .dbd.CH.sub.3 ; R.sup.2 .dbd.CH.sub.3 ; R.sup.3 .dbd..beta.-D-xylosyl PA0 B: R.sup.1 .dbd.CH.sub.3 ; R.sup.2 .dbd.CH.sub.3 ; R.sup.3 .dbd.H PA0 C: R.sup.1 .dbd.CH.sub.3 ; R.sup.2 .dbd.H; R.sup.3 .dbd..beta.-D-xylosyl PA0 D: R.sup.1 .dbd.H; R.sup.2 .dbd.CH.sub.3 ; R.sup.3 .dbd..beta.-D-xylosyl PA0 E: R.sup.1 .dbd.H; R.sup.2 .dbd.H; R.sup.3 .dbd..beta.-D-xylosyl PA0 FA-1: R.sup.1 .dbd.CH.sub.2 OH; R.sup.2 .dbd.CH.sub.3 ; R.sup.3 .dbd..beta.-D-xylosyl PA0 FA-2: R.sup.1 .dbd.CH.sub.2 OH; R.sup.2 .dbd.H; R.sup.3 .dbd..beta.-D-xylosyl
Pradimicin A was reported as BMY-28567 in Abstract No. 984 of the 27th Interscience Conference on Antimicrobial Agents and Chemotherapy, Oct. 4-7, 1987, New York, N.Y.
Pradimicins A, B, C, and the aglycone are disclosed in European Patent Application No. 277,621.
Pradimicins D and E, and their respective desxylosyl analogs are disclosed in our co-pending application, U.S. Ser. No. 203,776, filed Jun. 7, 1988, now U.S. Pat. No. 4,992,425, issued Feb. 12, 1991.
Pradimicins FA-1 and FA-2, their respective desxylosyl derivatives, N-alkyl derivatives thereof, and the aglycone are disclosed in our co-pending application, U.S. Ser. No. 269,821, filed Nov. 10, 1988, now U.S. Pat. No. 4,973,673, issued Nov. 27, 1990.
Two compounds, known as benanomicins A and B, were reported in J. Antibiot., 1988, 41 (6):807-811, and ibid, 41 (8): 1019-1028. Benanomicin B appears to be identical to pradimicin C, whereas benanomicin A has the following structure II: ##STR2## Desxylosyl benanomicin B was also disclosed but desxylosyl benanomicin A was not.